Systematic review and network meta‐analysis of mesenchymal stem cells in treating diabetic skin ulcers in animal models

Abstract

Background

Diabetic cutaneous ulcers often pose considerable challenges in the healing process. These challenges stem from factors including inadequate perfusion of the ulcer's surrounding environment, persistent inflammation, tissue damage and microbial proliferation. The existing standard treatment modalities prove insufficient in fully addressing the complex pathogenesis of these ulcers. As a novel approach, researchers are exploring cellular therapies employing mesenchymal stem cells (MSCs) for the treatment of diabetic skin ulcers. MSCs are readily found in various tissues, including bone marrow, adipose tissue, placenta, amniotic membrane, amniotic fluid and umbilical cord. However, the optimal source of MSCs for effectively treating diabetic skin ulcers remains a topic of ongoing discussion.

Methods

We conducted a comprehensive search of Embase, PubMed and Web of Science databases, spanning from their inception to November 2022. Subsequently, we rigorously screened the literature following predetermined inclusion and exclusion criteria and evaluated the quality of the selected studies using the SYRCLE scale. Finally, the included literature underwent analysis, employing the Bayesian school of thought-based R language. To ensure transparency and accountability, we registered this study with PROSPERO's International Systematic Review Prospective Registry, with the Registration ID: CRD42023387421.

Results

We included a total of 11 articles in our analysis, all of which were randomized controlled studies involving 218 animal models. Among these studies, two utilized adipose-derived MSCs, six employed bone marrow-derived MSCs, one utilized amniotic membrane-derived MSCs and three utilized umbilical cord-derived MSCs. Our network meta-analysis results revealed that there were no statistically significant differences in the healing rates of diabetic skin ulcers among MSCs derived from amniotic membrane, adipose tissue, umbilical cord and bone marrow on days 7–8, 10–12 and 12–14. Notably, according to the probability ranking table, the most effective treatment for diabetic wounds was found to be amniotic membrane-derived MSCs.

Conclusion

There was no statistically significant difference in the efficacy of MSCs derived from amniotic membrane, adipose, umbilical cord and bone marrow in the treatment of diabetic skin ulcers during the short-term observation period, and the probability ranking graphs indicate that amniotic membrane-derived MSCs may be the best choice for the treatment of diabetic skin ulcers.